The Human Immunodeficiency Virus Type 1 vif Gene: The Road from an Accessory to an Essential Role in Human Immunodeficiency Virus Type 1 Replication
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The vif (virion infectivity factor) gene is one of nine genes known to be expressed by human immunodeficiency virus (HIV)-1 (Wong-Staal and Gallo 1985; Haseltine 1988); vif and four other genes encode protein which are not structural components of virions but regulate viral replication to varying degrees (Haseltine 1988; Levy 1993). The two best-known viral regulatory genes, tat and rev, are essential for HIV-1 replication (Rosen et al. 1986; Sodroski et al. 1986b); in contrast, vif has been defined as an accessory gene because in initial studies its function was found to be dispensable for virus infection of transformed T cell lines (Sodroski et al. 1986a; Fisher et al. 1987; Strebel et al. 1987). After the initial description of vif and the effects of its ablation on virus replication (Sodroski et al. 1986a; Fisher et al. 1987; Strebel et al. 1987), very little research was done to further the understanding of the function of this viral gene product. Recently, however, a number of laboratories made the unexpected observation that vif is required for HIV-1 infection in its primary target cells, CD4-bearing T lymphocytes (Akari et al. 1992; Fan and Peden 1992; Gabuzda et al. 1992; Michaels et al. 1993; von Schwedler et al. 1993). This all-or-none dependence on the expression of vif for HIV-1 infection of peripheral blood lymphocytes (PBL) is illustrated in Fig. 1. These findings mandate the redefinition of vif as an essential gene for HIV-1 replication. We shall review the studies on the role of vif in HIV-1 infection and shall attempt to incorporate the results from different systems in the construction of a testable model for the mechanism of action of Vif. Because the cell-type dependence of Vif activity has become apparent only recently, early studies must be interpreted with these new variables in mind.
KeywordsHuman Immunodeficiency Virus Peripheral Blood Lymphocyte Equine Infectious Anemia Virus Virion Infectivity Factor Intracellular Viral Protein
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